Liver Fibrosis Stage Research Articles

The relationship between diabetes mellitus and non-alcoholic fatty liver disease: a clinical and instrumental paired study

To study the impact of type 2 diabetes mellitus (DM2) on the severity of liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). To conduct a paired case-control study 2989 patients were examined at the Federal Research Center of Nutrition, Biotechnology and Food Safety. Pairs were matched by gender and age and distributed into groups: NAFLD + DM2+ (n=313), NAFLD + DM2- (n=313) and a control group of patients without NAFLD and without DM2 (n=313). The severity of liver steatosis was determined by measuring the controlled attenuation parameter. The severity of liver fibrosis was determined by measuring the liver stiffness measurement. Body composition of the patients was determined using bioimpedance measurements. Indicators of lipid and carbohydrate metabolism, and the serum activity of liver enzymes was determined by standard biochemical methods. In NAFLD + DM2+ group compared to NAFLD + DM2- group, and in NAFLDM + DM2-compared to the control group, weight, BMI, waist and hip circumference, waist-to-hip ratio were higher, while in all. In NAFLD + DM2+ and NAFLD + DM2- groups the volume of fat mass directly correlated with the level of blood triglycerides (r=0.21), HbA1с (r=0.32) and fasting blood glucose (r=0.35), and inversely correlated with high-density lipoproteins (r=-0.19). In NAFLD + DM2+ group versus NAFLD + DM2- group severe steatosis (S3, 78% versus 59.4%; p<0.001) and severe fibrosis (F4, 8% vs 2.6%; p<0.001) was more common; 70% of patients in the NAFLD + DM2- group had no liver fibrosis according to elastography (F0), while in the NAFLD + DM2+ group only 43.2% of patients had no liver fibrosis (p<0.0001). When NAFLD is accompanied by DM2, there is an increase in total fat mass, the severity of steatosis and liver fibrosis, and an associated deterioration of lipid metabolism. More than half of these patients have various stages of liver fibrosis, which indicates the progressive nature of the disease.

Liver fibrosis is closely linked with metabolic-associated diseases in patients with autoimmune hepatitis.

This cross-sectional study aimed to investigate the impact of metabolic-associated diseases (MADs) on patients with autoimmune hepatitis (AIH). The study analyzed the clinical characteristics of 283 AIH patients who underwent liver biopsy between January 2016 and February 2022 in Ruijin Hospital, Shanghai, China. Among the identified AIH patients (n = 283), 87.3%, 23.0%, or 43.1% had MADs, non-alcoholic fatty liver disease (NAFLD), or severe fibrosis, respectively. The proportion of diabetes mellitus (DM) was significantly higher in patients with severe liver fibrosis than in those with mild or moderate fibrosis in the AIH cohort (31.1% vs. 18.0%, p < 0.05). Fibrosis was also more severe in patients with NAFLD than in those without (53.8% vs. 39.9%, p < 0.05). Age, Plts, IgG and the presence with MADs were identified as independent predictors of the severity of inflammation in AIH patients. Moreover, severe liver fibrosis (stages 3 to 4) was independently associated with male (OR, 2.855; p = 0.025), γ-GT (OR, 0.997; p = 0.007), and combination with MADs (OR, 4.917; p = 0.006). Furthermore, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients (OR, 2.445, p = 0.038). Concurrent MADs, common in AIH patients, is an independent risk factor for severe fibrosis or inflammation; of note, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients. While managing with AIH, routine assessment of co-existing MADs, especially DM, is also important.

Redox Homeostasis and Non-Invasive Assessment of Significant Liver Fibrosis by Shear Wave Elastography.

Hepatic fibrosis with various origins can be estimated non-invasively by using certain biomarkers and imaging-based measurements. The aim of our study was to examine redox homeostasis biomarkers and liver stiffness measurements for the assessment of significant liver fibrosis in different etiologies of chronic liver diseases. A cohort study consisting of 88 chronic liver disease patients of both sexes (age 49.1 ± 14.7 years) was performed. Cytokine profiles as well as redox homeostasis characteristics were determined. Liver fibrosis stages were assessed with shear wave elastography. The plasma levels of four cytokines showed no significant alteration between the four fibrotic stages; however, higher values were measured in the F2-4 stages. Free sulfhydryl group concentration, the marker of redox homeostasis, was lower in significant fibrosis (F0-F1: 0.36 ± 0.06 vs. F2-4: 0.29 ± 0.08 mmol/L, p < 0.05). Higher chemiluminescence values, as free radical-antioxidant parameters, were detected in advanced fibrosis stages in erythrocytes (F0-F1: 36.00 ± 37.13 vs. F2-4: 51.47 ± 44.34 RLU%). These data suggest that oxidative stress markers can predict significant fibrosis, with the aim of reducing the number of protocol liver biopsies in patients unlikely to have significant disease; however, their role in distinguishing between the certain fibrosis groups needs further studies.

Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B.

The progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent. Based on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests. Patients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively. Ultimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King's score, the model in the training cohort (AUC = 0.834, 95% CI 0.800-0.868, p < 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742-0.866, p < 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King's scores in all cohorts. This study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.

A combination model of CT-based radiomics and clinical biomarkers for staging liver fibrosis in the patients with chronic liver disease

A combined model was developed using contrast-enhanced CT-based radiomics features and clinical characteristics to predict liver fibrosis stages in patients with chronic liver disease (CLD). We retrospectively analyzed multiphase CT scans and biopsy-confirmed liver fibrosis. 160 CLD patients were randomly divided into 7:3 training/validation ratio. Clinical laboratory indicators associated with liver fibrosis were identified using Spearman's correlation and multivariate logistic regression correlation. Radiomic features were extracted after segmenting the entire liver from multiphase CT images. Feature dimensionality reduction was performed using RF-RFE, LASSO, and mRMR methods. Six radiomics-based models were developed in the training cohort of 112 patients. Internal validation was conducted on 48 randomly assigned patients. Receptor Operating Characteristic (ROC) curves and confusion matrices were constructed to evaluate model performance. The radiomics model exhibited robust performance, with AUC values of 0.810 to 1.000 for significant fibrosis, advanced fibrosis, and cirrhosis. The integrated clinical-radiomics model had superior diagnostic efficacy in the validation cohort, with AUC values of 0.836 to 0.997. Moreover, these models outperformed established biomarkers such as the aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis 4 score (FIB-4), as well as the gamma glutamyl transpeptidase to platelet ratio (GPR), in predicting the fibrotic stages. The clinical-radiomics model holds considerable promise as a non-invasive diagnostic tool for the assessment and staging of liver fibrosis in the patients with CLD, potentially leading to better patient management and outcomes.

Magnetic Resonance Elastography for Staging Liver Fibrosis in the Oncopig.

This pilot study investigated the feasibility of using magnetic resonance elastography (MRE) for the non-invasive detection and quantification of liver fibrosis in the Oncopig cancer model. Seven 8-week-old Oncopigs underwent alcoholic liver fibrosis induction and serial MRE imaging and liver biopsy at 1, 2, and 3 months post procedure. MRE was utilized to quantify liver stiffness, and liver fibrosis was histologically graded using the METAVIR system. The primary outcome measure was the capability to detect and quantify liver fibrosis using MRE with radiologic-pathologic correlation. Liver fibrosis induction, MRE imaging, and liver biopsy were successfully performed. MRE liver fibrosis was evident in 57% (4/7), 50% (3/6), and 40% (2/5) animal subjects 1, 2, and 3 months after fibrosis induction, with mean liver stiffness of 2.94, 3.25, and 2.91 kPa, respectively. Histological liver fibrosis was noted in 71% (5/7), 100% (5/5), and 100% (5/5) of animal subjects with available tissue samples. There was no significant statistical correlation between the MRE-measured liver stiffness and the METAVIR fibrosis scores. In conclusion, quantifiable liver fibrosis may be induced in the Oncopig. MRE has potential utility in non-invasively detecting liver stiffness in this large-animal preclinical model, though tissue biopsy was more sensitive in demonstrating disease.

Cardiovascular risk in US adults with nonalcoholic steatohepatitis (NASH) vs. matched non-NASH controls, National Health and Nutrition Examination Survey, 2017-2020.

NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status. A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables. A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude. Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk.

Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma.

Precise staging and classification of liver fibrosis are crucial for the hierarchy management of patients. The roles of lactylation are newly found in the progression of liver fibrosis. This study is committed to investigating the signature genes with histone lactylation and their connection with immune infiltration among liver fibrosis with different phenotypes. Firstly, a total of 629 upregulated and 261 downregulated genes were screened out of 3 datasets of patients with liver fibrosis from the GEO database and functional analysis confirmed that these differentially expressed genes (DEGs) participated profoundly in fibrosis-related processes. After intersecting with previously reported lactylation-related genes, 12 DEGs related to histone lactylation were found and narrowed down to 6 core genes using R algorithms, namely S100A6, HMGN4, IFI16, LDHB, S100A4, and VIM. The core DEGs were incorporated into the Least absolute shrinkage and selection operator (LASSO) model to test their power to distinguish the fibrotic stage. Advanced fibrosis presented a pattern of immune infiltration different from mild fibrosis, and the core DEGs were significantly correlated with immunocytes. Gene set and enrichment analysis (GSEA) results revealed that core DEGs were closely linked to immune response and chemokine signaling. Samples were classified into 3 clusters using the LASSO model, followed by gene set variation analysis (GSVA), which indicated that liver fibrosis can be divided into status featuring lipid metabolism reprogramming, immunity immersing, and intermediate of both. The regulatory networks of the core genes shared several transcription factors, and certain core DEGs also presented dysregulation in other liver fibrosis and idiopathic pulmonary fibrosis (IPF) cohorts, indicating that lactylation may exert comparable functions in various fibrotic pathology. Lastly, core DEGs also exhibited upregulation in HCC. Lactylation extensively participates in the pathological progression and immune infiltration of fibrosis. Lactylation and related immune infiltration could be a worthy focus for the investigation of HCC developed from liver fibrosis.

Ultrasonic Assessment of Liver Fibrosis Using One-Dimensional Convolutional Neural Networks Based on Frequency Spectra of Radiofrequency Signals with Deep Learning Segmentation of Liver Regions in B-Mode Images: A Feasibility Study.

The early detection of liver fibrosis is of significant importance. Deep learning analysis of ultrasound backscattered radiofrequency (RF) signals is emerging for tissue characterization as the RF signals carry abundant information related to tissue microstructures. However, the existing methods only used the time-domain information of the RF signals for liver fibrosis assessment, and the liver region of interest (ROI) is outlined manually. In this study, we proposed an approach for liver fibrosis assessment using deep learning models on ultrasound RF signals. The proposed method consisted of two-dimensional (2D) convolutional neural networks (CNNs) for automatic liver ROI segmentation from reconstructed B-mode ultrasound images and one-dimensional (1D) CNNs for liver fibrosis stage classification based on the frequency spectra (amplitude, phase, and power) of the segmented ROI signals. The Fourier transform was used to obtain the three kinds of frequency spectra. Two classical 2D CNNs were employed for liver ROI segmentation: U-Net and Attention U-Net. ROI spectrum signals were normalized and augmented using a sliding window technique. Ultrasound RF signals collected (with a 3-MHz transducer) from 613 participants (Group A) were included for liver ROI segmentation and those from 237 participants (Group B) for liver fibrosis stage classification, with a liver biopsy as the reference standard (Fibrosis stage: F0 = 27, F1 = 49, F2 = 51, F3 = 49, F4 = 61). In the test set of Group A, U-Net and Attention U-Net yielded Dice similarity coefficients of 95.05% and 94.68%, respectively. In the test set of Group B, the 1D CNN performed the best when using ROI phase spectrum signals to evaluate liver fibrosis stages ≥F1 (area under the receive operating characteristic curve, AUC: 0.957; accuracy: 89.19%; sensitivity: 85.17%; specificity: 93.75%), ≥F2 (AUC: 0.808; accuracy: 83.34%; sensitivity: 87.50%; specificity: 78.57%), and ≥F4 (AUC: 0.876; accuracy: 85.71%; sensitivity: 77.78%; specificity: 94.12%), and when using the power spectrum signals to evaluate ≥F3 (AUC: 0.729; accuracy: 77.14%; sensitivity: 77.27%; specificity: 76.92%). The experimental results demonstrated the feasibility of both the 2D and 1D CNNs in liver parenchyma detection and liver fibrosis characterization. The proposed methods have provided a new strategy for liver fibrosis assessment based on ultrasound RF signals, especially for early fibrosis detection. The findings of this study shed light on deep learning analysis of ultrasound RF signals in the frequency domain with automatic ROI segmentation.

Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis.

The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy. Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Extracellular NAD+ response to post-hepatectomy liver failure: bridging preclinical and clinical findings

Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+’s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.

Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C.

Liver fibrosis stage based on the four factors (FIB-4) score or Forns index in adults with chronic hepatitis C.

The relationship between CXCR6+CD8+T cells and clinicopathological parameters in patients with primary biliary cholangitis.

CXCR6+CD8+T cells have been implicated in the pathogenesis of various liver and autoimmune diseases. However, their involvement in primary biliary cholangitis (PBC) has not been elucidated. We used immunohistochemistry and flow cytometry to quantify CXCR6+CD8+T cells in hepatic tissue and peripheral blood samples obtained from CXCR6+CD8+T cells obtained from PBC patients. Then, we performed comprehensive statistical analyses to access the correlation between the abundance of these cells and clinical as well as pathological data across different stages of PBC. Our research revealed that CXCR6+ cell frequencies in CD3+CD8+T cells from PBC patients significantly exceeded that of healthy controls (HCs) (2.24 vs. 0.61%, p < 0.01). A similar pattern emerged for hepatic CXCR6+CD8+T cell counts, which were notably higher in the PBC cohort compared to HCs. Our cohort consisted of 118 PBC patients, categorized into 62 early-stage (E-PBC) and 56 late-stage (L-PBC) cases. Notably, significant disparities existed between these groups in terms of liver enzyme and lipid profile levels (p < 0.05), with no notable differences observed in gender, age, blood counts, cholesterol levels, or autoantibodies (p > 0.05). Intriguingly, the quantity of hepatic CXCR6+CD8+T cells per high power field (HPF) was significantly elevated in both E-PBC and L-PBC patients as opposed to normal liver samples, indicating a substantial increase in these cells across all stages of PBC (p = 0.000). Spearman's rank correlation analysis showed a positive correlation between CXCR6+CD8+T cell counts and serum levels of Alkaline Phosphatase (AKP) and Gamma-Glutamyl Transferase (GGT), ANA, IgG and IgM, while revealing a negligible correlation with Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). Subsequent findings indicated significant variances in CXCR6+ cell numbers not only among different PBC stages but also across various degrees of inflammation and fibrosis (p ≤ 0.007). In a follow-up study post-Ursodeoxycholic Acid (UDCA) treatment, stark differences were identified in biochemical and immunohistochemical profiles between responder (31 patients) and non-responder (33 patients) groups (p < 0.05). A Wilcoxon rank-sum test further demonstrated a significant difference in the level of hepatic CXCR6+CD8+T cells between these two response groups (p = 0.002). CXCR6+CD8+T cells play a vital role in the pathogenesis of PBC, exhibiting correlations with the extent of inflammation, staging of liver fibrosis, and response to pharmacological interventions in PBC patients.

Incorporating artificial intelligence in portable infrared thermal imaging for the diagnosis and staging of nonalcoholic fatty liver disease.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is one of the most prevalent chronic liver diseases worldwide. Thermal imaging combined with advanced image-processing and machine learning analysis accurately classified disease status in a study on mice; this study aimed to develop this tool for humans. This prospective study included 46 patients who underwent liver biopsy. Liver thermal imaging was performed on the same day as liver biopsy. We developed an image-processing algorithm that measured the relative spatial thermal variation across the skin covering the liver. The texture parameters obtained from the thermal images were input into the machine learning algorithm. Patients were diagnosed with MASLD and stratified according to nonalcoholic fatty liver disease activity score (NAS) and fibrosis stage using the METAVIR score. Twenty-one of 46 patients were diagnosed with MASLD. Using thermal imaging followed by processing, detection accuracy for patients with NAS >4 was 0.72.

Mechanisms of high cardiovascular risk in patients with nonalcoholic fatty liver disease

Aim. To optimise the curation of patients with a comorbid course of nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) to explore pathogenetically-based targets of high cardiovascular risk (CVR) formation. Materials and methods. An open comparative study was conducted with the formation of a cohort of 126 patients with comorbid course of NAFLD and CVD with different stages of liver fibrosis, who were divided into comparison groups according to SCORE-2 and SCORE-2-OR. Collection of complaints, medical and life history, examination, general laboratory investigations and examination of hormonal status, abdominal ultrasound, EchoCG and liver elastometry to assess the severity of fibrosis were performed. Work with the study data and graphical analysis was performed using Microsoft Office 2019 software package statistical analysis using STATISTICA 12.0. Results. SCORE-2 risk increased with increasing age of patients (z=-5.29; p0.01). The most common non-cardiovascular co-morbidities in the study sample were cholelithiasis in 35 (66.78%) patients. Soluble leptin receptor levels were lower (z=-8.60; p0.01) and leptin resistance index was higher (z=-5.95; p0.01) in the higher cardiovascular group. Corresponding data were also obtained when the changes in insulin resistance index were calculated and analysed (z=-2.15; p0.01). Fibrosis stage was higher, in patients with higher CVR (z=-3.488; p0.01), while no statistically significant difference in steatosis level was recorded. According to transient elastometry, patients taking statins had lower levels of fibrosis (z=-3.747; p0.01) and hepatic steatosis (z=-3.379; p0.01). Conclusions. The most common pathology is arterial hypertension. Gallstone disease and type 2 diabetes mellitus are often found in patients with a comorbid course. The risk of comorbid pathology and CVD increases with age. Formation of advanced stages of liver fibrosis, hyperinsulinaemia and leptin resistance phenomenon are associated with higher CVR according to SCORE-2 and SCORE-2-OR. The syndrome of increased intestinal permeability is a possible mechanism of increased CVD in patients with NAFLD.

A Cross-Sectional Study on Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus and the Association of Risk Factors with Liver Steatosis and Fibrosis Stages

A Cross-Sectional Study on Non-Alcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus and the Association of Risk Factors with Liver Steatosis and Fibrosis Stages

Correlations Between Viro-Immunologic Status of the Newly Diagnosed Patient with HIV Infection and Liver Damage

Abstract Liver damage can be a direct consequence of human immunodeficiency virus infection or indirect mechanisms triggered by human immunodeficiency virus. Hepatic fibrosis may be present in patients newly diagnosed with HIV infection or in those with viro-immunologic failure after initiation of antiretroviral therapy. In the present study we evaluated biologically and viro-immunologically the 351 patients newly diagnosed with HIV infection in the Regional Center Constanta between 01.01.2015 and 31.06.2024, subsequently re- evaluated one year after diagnosis and institution of specific medication. Liver fibrosis stage was assessed using APRI, FIB4 and FORNS scores. The cohort comprised 351 patients, 313 with HIV monoinfection. The mean age at diagnosis was 36.09 years, predominantly male (237 patients). The median CD4+ cell count was 269.5 cells/mm3, and the median HIV-RNA was 164 x103 copies/mL. Most cases were CDC staged A2 (91 cases) and C3 (77 cases). Patients with HIV monoinfection showed a significant association between CD4+ cell level and ALT (p=0.026) and AST (p&lt;0.001), respectively. We observed statistically significant correlation between AST and viral load values (p=0.003 in monoinfection and 0.042 in coinfection). APRI, FIB4 and FORNS scores averaged higher in the coinfected group compared to the HIV monoinfected group. Statistically significant associations were found between APRI, FIB4, FORNS scores and CD4+ cell counts and HIV viral load values, respectively.

A novel model based on serum N-glycan markers for evaluating stage of liver necroinflammation in treatment-naïve chronic hepatitis B patients.

This study aimed to establish a novel noninvasive model based on the serum N-glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N-glycan profiles of the sera of 295 treatment-naïve CHB patients were analyzed. N-glycan profiles were tested for different liver necroinflammation stages using DNA sequence-assisted fluorophore-assisted carbohydrate electrophoresis. A serum N-glycan model named N-glycan-LI(NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune-tolerant [IT] and inactive-carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune-active, and had the highest SPof 93.94% in grey zone IT + IC. N-glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve-treatment patients with CHB.

Noninvasive assessment of liver fibrosis in mini pigs using an 18F–AlF-NOTA-RGD2 PET/CT molecular probe

To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.

Quality Assurance of Point and 2D Shear Wave Elastography through the Establishment of Baseline Data Using Phantoms.

Ultrasound elastography has been available on most modern systems; however, the implementation of quality processes tends to be ad hoc. It is essential for a medical physicist to benchmark elastography measurements on each system and track them over time, especially after major software upgrades or repairs. This study aims to establish baseline data using phantoms and monitor them for quality assurance in elastography. In this paper, we utilized two phantoms: a set of cylinders, each with a composite material with varying Young's moduli, and an anthropomorphic abdominal phantom containing a liver modeled to represent early-stage fibrosis. These phantoms were imaged using three ultrasound manufacturers' elastography functions with either point or 2D elastography. The abdominal phantom was also imaged using magnetic resonance elastography (MRE) as it is recognized as the non-invasive gold standard for staging liver fibrosis. The scaling factor was determined based on the data acquired using MR and US elastography from the same vendor. The ultrasound elastography measurements showed inconsistency between different manufacturers, but within the same manufacturer, the measurements showed high repeatability. In conclusion, we have established baseline data for quality assurance procedures and specified the criteria for the acceptable range in liver fibrosis phantoms during routine testing.